Continuing the present study of the mechanism which balances the tissue need for oxygen with the production of red blood cells. The most appealing hypothesis involves the production and action of an erythropoietin hormone, the so-called erythropoietin. It is suggested that the oxygen tension in some specialized site, most likely the kidney, controls the production or release of this hormone. Following its release it is carried to the bone marrow where it controls the rate with which stem cells are differentiated into pronormoblasts. These pronormoblasts will divide and mature into adult red cells with the primary function of transporting oxygen to the tissues. This feedback circuit provides a simple regulating mechanism for red cell production. The proposed studies are designed to test each element in the chain which constitutes the feedback circuit, especially the effect of erythropoietin in the bone marrow and the effect of oxygen tension in the kidney.